Amyl-cresols and process for making



, nols or other cresols;

Patented Jan. 20, 1931 T D STATES PA1-ENT' Q1=F iOSEPH msHALL, or nor'rmenm, ENGLAND, 'nssrenon'ro noo'r's 1 m Dane eomrm tmrrrmoi' Norrmenam, sustain), A comramz or eamr Banana mr cnnsotsann raocnss ron' mine Io Drawing. Application filed December 20,

This invention relates to the production of monohydric phenols and aims at producm bodies possessing every high phenol coe ficient and having a toxic action of such a tiseptic and disinfectant properties. i

It has been recognized that the introduction of a methyl group into the molecule of.

cresol, the ketone produced may be reduced to a methyl n-amyltphenolpossessing avphenol coefiicient of about 280and' with a toxicity which is very low when compared with that of phenol or the cresols, and, as a matter of fact, it is als'ofound that other normal amyl cresols have a phenol eoeflicient which is very large in comparison withthat of known phe- Thus, the phenol coeflicient of G-n-amyl-o-cresol (OHzOH :CJL =1:2:6) is 250, and that of 4-n amylio-cresol I (OH:CH,:G5I-In71:2:4) is '300, and that of 2-n-amyl-p -cresol v :GH; :C5H11=1 :4 :2) c

It will be appreciated that even if it had been known that a normal amyl group could, by the method herein described, be introduced into the nucleusv of a cresol, itcould not be foreseen that the introduction of that radicle would so considerably increase the antiseptic power, and certainly itcould not be foreseen that the introductionof the said group into. a particular. position in metacresol would result in the production of a body with a phenol coeflicient of 280. Thus'according to the present invention, a cresyl n-valerate; isconverted into a normal amyl cresol by subjecting the ester totthe action-of aluminum chloride for a short time and reducing the products. It is found most convenient to employ rather more than one molecular uantity of anhydrous aluminum chloride. s a result of the action of alumi: num chloride, the n-valeryl group is caused to move and in the case of m-cresyl n-valerate,

1929, serial, No. 415,618, and in Great Britain larch 26,182!

hydroxyl group and 1p ara to the methyl group.

;This reaction 1s shown by the following equation: low order that they are of great value as '7 therapeutic substances with considerable anvaleryl m-cresoL; In the case of o-creisyl n-valerate a mixture of two ketones is produced, in one of vl which m-cresyl valeratm group., In each case the ketone so .fOrmedQand also fln valeryl-p-cresol- (in which the nvaleryl group-iso'rtho to the hydroxyl group) is reduced to an-amyl cresol in which the n- A amyl group occupies'the'same position as the original n-va'lerylgroup. 'Inthe case of the I productionfof n-amyl meta cresolthe' revaleryl-m-cresol amyl m-cresol 1 it'takes up'a position which is ortho to the i v the valeryl' group is ortho'to'the hydroxyl I group andin the other, para to the hydroxyl a "The resultant n-amyl cresols, as already mentioned, possess very high .phenol coefficients, viz., between 250 and 300. I I

In order that the. invention may be clearly understood and readily carried into efiect, some practicalmethods of carrying out the processaccording to the invention will now be described in. somewhat greater detail by way of example. v

hydrochloric acid is added and steam is blown through the mixture. After cooling, an oil separates and this is distilled in vacuum. Practically the whole of the material boils at about 152 to 154 C. under 15 mm. pressure. It may be purified by cooling in a freezing mixture and separating a small quantity of oily material, and .the crystals melt at about 60 C. 120 parts of this ketone, which is n-vale-ryl-meta-cresol, are mixed with 400 parts by weight of zinc amalgam, and boiled under a reflux condenser with a sufiicient quantity of a mixture of equal parts by weight of water, alcohol, and concentrated hydrochloric acid. The addition of the alcohol materially influences the time taken for the ketone to be completely reduced. When this reduction is complete, steam is blown through the mixture to remove the alcohol,

which may be recovered for use in a subsequent batch, and then the reduction mixture is allowed to cool andthe 6-n-amyl-metacresol is extracted with ether and purified by fractional distillation. It boils at 137 to 139 C. under 15mm. pressure. It may be purified by recrystallization from petrol ether, using a freezing mixture, and separating the crystals by filtering at a low tem .perature so as to separate a small quantity of oily material. The product so obtained melts at about .24 to 25 C. and possesses a phenol coefiicient of about 280. 1

Example 2 In producing n amyl-o-cresols, equal parts by weight of o-cresyl n-valerate and aluminum chloride. are mixed and heated quickly to 160 to 170 C., which temperature is maintained for one and a half hours, the mixture being stirred occasionally at the beginning of the operation. After cooling, the mass is heated with dilute hydrochloric acid on a steam bath or by blowing steam into it until the practically solid mass has been converted into a mobile oil which is separated from the dilute hydrochloric acid and distilled in Vacuo. Two main fractions are collected, the first at about 140 to 150, which is chiefly 6-n-valeryl-o-cresol (OH: CH CO.G H,=1 2 6),

and the second fraction at about 200 to 205. The lower fraction solidifies on cooling in a freezing mixture and it may be freed at a low temperature from adherent oil by draining on a filter pump. This ketone, when pure, melts at about 18.

- The higher fraction maybe purified by recrystallization from benzene or other suitable solvent, and this ketone, which is 4-nvaleryl-o-cresol is thus obtained as colourless prisms which have a melting point of about 103 to 104.

Example 3 In order to produce 2-n-amyl-p-cresol (0H: CH G H =1 4 2) the 2-n-valerylp cresol made by the known methods is boiled under a reflux condenser with 3 times its weight of amalgamated zinc and a sufficient quantity of'the alcoholic acid mixture described in Example 1, and when reduction is complete, the amyl p-cresol may be separated from the reduction mixtureby any convenient process, such as that described in Example 1, and it may be purified by distillation'under reduced pressure and by crystallization at a low temperature. When pure, 2-n-a1nyl-p-cresol hasfa phenol coeflicient of about 250, and a melting point of 10.

1. The process for the production of a normal amyl cresol which consists in effecting a reaction between acresyl n-valerate and aluminum chloride 3 and reducing the resulting ketone.

2. The process for'the production of a normal amyl cresolv which consists in effecting a reaction between a cresyl n-valerate and a small excess over a inolecularproportion of aluminum chloride and reducing the resulting ketone. q

3. The process for the production of a normal amyl cresol which consists in reducing a normal valeryl cresol by means of amalgamated zinc and hydrochloric acid.

4. The process for the production of a normal amyl cresol which consists in effecting a reaction between a cresyl n-valerate and aluminum chloride and reducing the resulting ketone by means of amalgamated zinc and hydrochloric acid.

5. The process for the production of a normal amylderivative of a phenol which consists in effecting a reaction between metacresyl valerate and aluminum chloride an reducing the resulting ketone.

6. The process for the production of a normal amyl derivative of a phenol'which consists in efi'ecting a reaction between metacresyl valerate and aluminum chloride and reducing'the resulting keton'e by means of amalgamated zincand hydrochloric acid.

"2'. The process for the production of a normal amyl derivative of a phenol which consists in reducing valeryl meta-cresol by means of amalgamated zinc and hydrochloric acid.

' amyl-m-cresol' 'which consists in'mixing equal parts by ride and reducin nuin chloride,'heatin 8. The process for-the reduction of 6-11- am l-m-cresol (OHiC ,-:C,H =1:3:6) which consists'in effecting a reaction between meta-cresol n-valerate and aluminum chloth-iesulting normalvaleryl-meta-creso by means of amalgamated zinc and hydrochloric acid. a

9. The process for the production of 6-n- (OH:CH:.G,H =1:3:6)

n-valerate and alumithe mixture until the and reducing the reweight of meta-cresol reaction is complete sulting normal-laleryl-meta-cresol by mixing with zinc amalgam and boiling with a mixture of equal parts by weightofwater, alcohol and concentrated hydrochloric acid.

10. A therapeutic substance com rising a normal amyl cresol, said substance aving a phenol coefiieient between 250 and 300.

11. A therapeutic substance comprising a normal amyl meta cresol, said-substancehaving a phenol coefiicient of about 280.

12. A therapeutic substance comprising 6- n-amyl-m-cresol (OH CH C 1 3 6) said substance havin in the pure condition, a phenol coeflicient 0? about 280.

13. The process for the production of normal amyl ortho cresols WhlCll consists in efiecting a reaction between ortho cresyl nvalerate and aluminum chloride, separating the ketones formed and reducing said ketones separately by means of amalgamated zinc and hydrochloric acid.

; having a phenol co-eflicient of between 14. The process for the normal amyl para-cresol w ich consists in reducing a normal valeryl para-cresol by means of amalgamated zinc and hydrochloric aci i 15. A therapeutic substance comprising a normal amyl ortho-cresol, said substgncz a on roduction of a 250 and 300.

16. A therapeutic substance comprising 2- n-amyl-para-cresol a I (OHiGHgZCn 11=1:4:2),

said substance having, in the pure condition, a henol co-efiicient of about 250. witness whereof I hereunto subscribe my name this 6th day of December, 1929.

, JOSEPH MARSHALL. 

